Grant Information

UNCOVERING THE ROLE OF MICROBES IN HEALTH AND DISEASE

Sponsoring Institution National Institute of Food and Agriculture
Status COMPLETE
Funding Source HATCH
Division NIFA Formula
Reporting Frequency Annual
Project Director Slupsky, Carolyn
Accession Number 1021411
Project Number CA-D-XXX-2088-H
Dates 2019-11-29 - 2024-09-30
Animal Health Component 50%
Performing Department Nutrition
Recipient Organization UNIVERSITY OF CALIFORNIA, DAVIS
410 MRAK HALL
DAVIS,CA 95616-8671
Keywords candidatus liberibacter
metabolism
microbiome
nutrition
systems biology
transcriptomics
Research Effort Applied (50%)
Basic (50%)
Developmental (0%)
Classification Parameters
Knowledge AreaSubject of InvestigationField of SciencePercent
702 - Requirements and Function of Nutrients and Other Food Components 4010 - Bacteria 1010 - Nutrition and metabolism 20%
212 - Pathogens and Nematodes Affecting Plants 999 - Citrus, general/other 1010 - Nutrition and metabolism 15%
212 - Pathogens and Nematodes Affecting Plants 999 - Citrus, general/other 1060 - Biology (whole systems) 15%
211 - Insects, Mites, and Other Arthropods Affecting Plants 999 - Citrus, general/other 1060 - Biology (whole systems) 10%
701 - Nutrient Composition of Food 5010 - Food (not readily associated with specific plant and animal products) 1010 - Nutrition and metabolism 10%
702 - Requirements and Function of Nutrients and Other Food Components 4010 - Bacteria 1050 - Developmental biology 10%
702 - Requirements and Function of Nutrients and Other Food Components 4010 - Bacteria 1060 - Biology (whole systems) 10%
702 - Requirements and Function of Nutrients and Other Food Components 4010 - Bacteria 1100 - Bacteriology 10%
Non-technical Summary

This project supports the mission of the Agricultural Experiment Station by addressing the Hatch Act area(s) of: plant and animal production, protection, and health; human nutrition.The goal of this project is to understand the role that microbes play in directing metabolism. By mechanistically understanding how microbes can change metabolism, there is an opportunity to create therapies that counteract the effect of the microbe (in the case that the microbe is doing harm to the host), or mimic the effect of the microbe (in the case that the microbe is beneficial).In this project we are studying two areas. One in plant health and the other in human health. In the project on plant health, we are performing experiments to mechanistically understand how the bacterium Candidatus Liberibacter asiaticus (CLas) impacts citrus metabolism both in the early and late stages of disease. This work is important for developing biomarkers for early detection of the disease, and also for informing of potential metabolic pathways that may be targeted to enhance plant defense. We are also studying the effect of this bacterium on insect metabolism, to further inform of potential pathways that may be manipulated to either stop acquisition or transmission of the bacterium by the insect.In the project on human health, we are studying the effect of different food nutrients on the microbiome, to understand how this may impact human health and future development of chronic disease. Here, we have several projects where we are studying the effect of different levels of protein in infant formula on the infant microbiome and metabolism. We are also looking at how components of milk (such as the milk fat globule membrane (MFGM), lactoferrin, or oligosaccharides) impact the infant microbiome and ultimately infant health both immediately and over the long term.In a separate project, we are studying the mechanism of how cognition is affected by micronutrient deficiencies or environmental exposures, and why males are more susceptible than females.These lines of research will help us understand the inter-kingdom connection between microbes and their host, provide important translatable information for the general public on maternal and infant nutrition, and ultimately help us find ways to prevent or treat various diseases in both plants and humans.

Goals / Objectives

The overall goal of this project is to understand the role that microbes play in defining health, how they are responsible for altering host metabolism, and how food or nutrients can affect their metabolism which in turn can affect the metabolism of the host. This project is focused in two areas: (A) human health: how the gut microbiome is modulated by diet, and how this diet alters human metabolism; and (B) plant health: how the microbiome contributes to plant defense, and how pathogens affect host metabolism. The goals are:

  1. To measure the impact of diet on metabolic health and development of the microbiome in infants.
  2. To measure the effect of maternal prenatal exposures on maternal and child metabolic health and microbiome.
  3. To measure the effect of fiber, polyphenols and other components on the microbiome and host metabolism.
  4. To measure the effect of C. Liberibacter and other citrus pathogens (CTV and S. citri) on citrus plant metabolism, defense, and microbial communities in the soil and on the plant which will allow us to understand the mode of pathogenicity of the bacterium, and highlight ways to direct efforts at strengthening host response or creating new strategies to mitigate the effect of the pathogen.
  5. To validate a set of biomarkers for early detection of C. Liberibacter that may allow detection earlier than gold standard qPCR-based methods.
  6. To participate in outreach to government regulatory agencies, and industry regarding HLB and ways to detect the disease in its early stages.
Methods (unparsed)

To measure the impact of diet on the microbiome and host metabolism, several techniques will be used that will include metabolomics, transcriptomics, proteomics and fecal ecology. For metabolomics measurement, urine, feces, blood and tissue will be collected and NMR-based metabolomics will measure a suite of metabolites including sugars, amino acids, organic acids, nucleic acids, vitamins, and other compounds. For transcriptomics measurement, blood and/or tissue will be collected and RNA purified using commercially available RNA purification kits. For proteomics, we will perform the standard Western Blots to target specific proteins, and for a more comprehensive approach, we will prepare and submit samples to the proteomics core at UC Davis. For bacterial ecology, samples will be prepared using commercially available DNA purification kits. For transcriptomics and bacterial ecology, sequencing will be performed at the UC Davis Genome Center. DNA, RNA and metabolites will be analyzed using commercially available software.For measurement of the impact of pathogens on plant metabolism, leaves will be extracted for metabolites and RNA, and these will be subjected to metabolomics and transcriptomics measurements (as described above) to correlate metabolites with specific metabolic pathways and determine how plant metabolism is affected by specific pathogens. Subsequently, biomarker profiles will be validated using field trees by comparing with other early detection systems.

Methods
To measure the impact of diet on the microbiome and host metabolism, several techniques will be used that will include metabolomics, transcriptomics, proteomics and fecal ecology. For metabolomics measurement, urine, feces, blood and tissue will be collected and NMR-based metabolomics will measure a suite of metabolites including sugars, amino acids, organic acids, nucleic acids, vitamins, and other compounds. For transcriptomics measurement, blood and/or tissue will be collected and RNA purified using commercially available RNA purification kits. For proteomics, we will perform the standard Western Blots to target specific proteins, and for a more comprehensive approach, we will prepare and submit samples to the proteomics core at UC Davis. For bacterial ecology, samples will be prepared using commercially available DNA purification kits. For transcriptomics and bacterial ecology, sequencing will be performed at the UC Davis Genome Center. DNA, RNA and metabolites will be analyzed using commercially available software.For measurement of the impact of pathogens on plant metabolism, leaves will be extracted for metabolites and RNA, and these will be subjected to metabolomics and transcriptomics measurements (as described above) to correlate metabolites with specific metabolic pathways and determine how plant metabolism is affected by specific pathogens. Subsequently, biomarker profiles will be validated using field trees by comparing with other early detection systems.
Project Timeline Tracking

Outputs

Target Audience
The target audience of my research was citrus growers and the citrus industry on the impact of Candidatus Liberibacter asiaticus (CLas) on the insect and plant. My target audience was also the diary industry, physicians, and the general public on the work my group has been doing on the impact of milk components on the microbiome and health. Over the past year, my outreach was lower than usual due to the COVID-19 pandemic. However, I was able to reach citrus growers and serve the citrus industry through serving on the Organic HLB Advisory Board throughout 2020. My service included meetings and writing of letters of support. Other ways that I reached target audiences included speaking at various events. In January I spoke at the Center for Emerging & Neglected Diseases (CEND) symposium regarding our work on huanglongbing (HLB), where the goal was to educate innovators, other researchers and the general public about emerging and neglected infectious diseases. In July, I spoke at the virtual Institute of Food Technologists (IFT) meeting to educate industry and other researchers on our work on the link between dairy constituents and infant health. In December, I participated as a respondent for a session on the Gut Microbiome for the American Association for the Advancement of Science (AAAS), which will be aired in February of 2021. Finally, I participated as a panel member for the Food Ag Ideas (FAI) week that was led by Grow North in December in a session concerning the Nexus of Food and Health. The audience included individuals from Fortune 500 companies, entrepreneurs in the food business, growers, innovators, non-profit organizations, and investors from throughout the United States.

Changes / Problems
Nothing Reported

Training & Professional Development
Over the period of review, I trained graduate students (Aidong Wang, Caitlin French, Laurynne Coates, Hanna Lee, Christopher McNeil, Mariana Parenti, Yu Hasegawa, Jules Larke, Rachel Lombardi, Kirsten Roslund, Sydney Thomas, Eduardo Romo, and Brooke Wickman), post-doctoral fellows (Emily Padhi, and Shannon McClorry). Laurynne Coates graduated with her PhD in June of 2020, and is currently a post-doctoral fellow at the USDA. Christopher McNeil and Hanna Lee graduated with their PhD in September of 2020. Christopher is a post-doctoral fellow at Santa Clara University, and Hanna is a post-doctoral fellow in my lab at UC Davis. Yu Hasegawa graduated in December of 2020, and is currently a post-doctoral fellow at the University of Wisconsin.

Dissemination Streams
Over the past year, my dissemination to communities of interest was lower than usual due to the COVID-19 pandemic. I reached target audiences through speaking at various virtual events. In January I spoke at the Center for Emerging & Neglected Diseases (CEND) symposium regarding our work on huanglongbing (HLB), where the goal was to educate innovators, other researchers and the general public about emerging and neglected infectious diseases (I performed this remotely due to a surgery that precluded my being able to travel to Berkeley). In July, I spoke at the virtual Institute of Food Technologists (IFT) meeting to educate industry and other researchers on our work on the link between dairy constituents and infant health. In December, I participated as a respondent for a session on the Gut Microbiome for the American Association for the Advancement of Science (AAAS), which will be aired in February of 2021. Finally, I participated as a panel member for the Food Ag Ideas (FAI) week that was led by Grow North in December in a session concerning the Nexus of Food and Health. The audience included individuals from Fortune 500 companies, entrepreneurs in the food business, growers, innovators, non-profit organizations, and investors from throughout the United States. I also performed interviews with Science writers for magazines (Christina Szalinski, freelance writer, Marta Ustyanich, STRONG fitness magazine, and Katherine Wu, Smithsonian),?

Next Reporting Steps
Nothing Reported


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